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(Circulation Research. 2003;93:271.)
© 2003 American Heart Association, Inc.

Editorials

Homocysteine, a Proinflammatory and Proatherosclerotic Factor

Role of Intracellular Reactive Oxygen Species

Valérie B. Schini-Kerth

From the UMR CNRS 7034, University Louis Pasteur Strasbourg, Faculty of Pharmacy, Illkirch, France.

Correspondence to Valérie B. Schini-Kerth, PhD, Professor of Pharmacology, Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, UMR CNRS 7034, Université Louis Pasteur de Strasbourg, Faculté de Pharmacie, 74, route du rhin B.P. 60024, 67401 Illkirch, France. E-mail schini@aspirine.u-strasbg.fr

Key Words: homocysteine • monocyte chemoattractant protein-1 • interleukin-8 • reactive oxygen species • human monocytes

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In 1969, McCully first described the association of hyperhomocysteinemia and vascular disease in a patient with elevated levels of homocysteine in plasma and urine due to a rare genetic deficiency of homocysteine metabolism.¹ A large number of clinical studies have indicated that mild hyperhomocysteinemia, which occurs in approximately 5% to 7% of the general population, is also associated with vascular disease including coronary artery, cerebrovascular, and peripheral arterial occlusive diseases.^2,3 Elevated plasma levels of homocysteine are considered as an independent risk factor for atherothrombotic disease.⁴ Both experimental and clinical data suggest that elevated plasma concentrations of homocysteine might accelerate the development of atherosclerotic lesions to advanced atherosclerotic plaques, which are sites of endothelial erosion and rupture triggering the formation of occlusive mural thrombi and ischemic events.

Homocysteine is an intermediate sulfur-containing amino acid formed during the intracellular metabolism of methionine, an essential amino acid supplied by dietary proteins (see Figure).² Once homocysteine is formed, it may be recycled to methionine after remethylation by two different pathways. The first one involves methionine synthase, an enzyme that uses vitamin B₁₂ (cobalamin) as an essential cofactor and N⁵-methyl-tetrahydrofolate as the methyl donor. The second pathway, which occurs exclusively in hepatic tissue, involves the enzyme betaine-homocysteine methyltransferase. Homocysteine may also be converted to cystathionine by cystathionine ß-synthase, a vitamin B₆-dependent enzyme, which is subsequently hydrolyzed to form cysteine by cystathionine -lyase. Cysteine, in turn, can be used to synthesize the antioxidant glutathione or be further metabolized to sulfate and excreted in . . . [Full Text of this Article]

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